The long-term goals of this research project are to detail the possible role of the cAMP signaling system in Bipolar Disorder. A genetic association study of polymorphisms in twenty different candidate genes representing the cAMP signaling components in humans is proposed, using well-characterized populations of Bipolar Type I Disorder and Bipolar Type II Disorder. These genes were selected because of existing evidence that cAMP signaling may be perturbed in Bipolar Disorder and because cAMP signaling underlies many types of behavior, including learning and memory, in model organisms. Researchers from the Massachusetts General Hospital and the Baylor College of Medicine will collaborate on this project, with researchers from MGH facilitating the exchange of DNA samples from well-characterized Bipolar Disorder patients and assisting with the interpretation of clinical relevance, and researchers from the Baylor College of Medicine performing the genetic analyses. These translational studies are designed to systematically and critically test the hypothesis that alterations in one or more cAMP signaling genes are involved causally in the behavioral abnormalities associated with Bipolar Disorder. Public Health Relevance: Bipolar Disorder is a prevalent brain disorder. The studies proposed here will help to elucidate the genetic basis for the disease.